Currently, more than one million U.S. women each year seek treatment for infertility. This number continues to increase, as more women delay childbirth until later ages, adoption becomes increasingly difficult, and the recognition of new, sophisticated technologies for assisted reproduction becomes more widespread. Recently, there has been increasing concern regarding the potential neoplastic effects of the powerful ovulatory stimulants used in the treatment of infertility. In a recently completed study, we observed a strong increase in risk of ovarian cancer associated with use of clomiphene citrate for greater than one year (adjusted RR=11.1, 95% CI 1.5-82.3). The biological plausibility of an effect of ovulation-inducing agents on risk of ovarian cancer, the increasing prevalence of exposure to these drugs, and the limited data currently available all indicate a strong need for further research. We propose to conduct a population-based case-control study examining risk of ovarian cancer associated with the use of fertility drugs, including ovulation-inducing agents such as clomiphene citrate and exogenous gonadotropins. Cases will be women aged 35-54 diagnosed with ovarian cancer from May 1 1995- April 30, 1998 in 3 study sites. Controls will be similarly aged women selected by random digit dialing in each of the study sites. Details regarding medical evaluation and/or treatment for infertility will be elicited at in-person interview, as will information regarding family cancer history and other known and potential risk factors for ovarian cancer. Information regarding the types, dosage and duration of infertility treatments received will also be abstracted from infertility clinic medical records. Blood samples will be collected at the time of interview and white cells will be stored to enable future genetic testing (e.g., for the presence of the BRCA1 gene) to examine the effect of inherited genetic susceptibility to ovarian cancer on the relationship between fertility drug use (as well as other environmental factors) and risk of this disease. Our proposed study is efficient as it will use as controls, at no cost to this study, approximately 2000 women interviewed as controls for an MCHD- funded multi-center case-control study of breast cancer (the Women's CARE study) which will be conducted concurrently with and in the same geographic areas as this study. Further, the population-based case-control design of our study will enable us to assess whether infertile women without exposure to ovulation-inducing drugs are at an increased risk of ovarian cancer, or, alternatively, whether any increase in risk of ovarian cancer associated with infertility may be due to the use of fertility drugs.